Patients taking psilocybin to treat depression show reduced symptoms weeks after treatment following a ‘reset’ of their brain activity.

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The findings come from a study in which researchers from Imperial College London used psilocybin – the psychoactive compound that occurs naturally in magic mushrooms – to treat a small number of patients with depression in whom conventional treatment had failed.

In a paper, published in the journal Scientific Reports, the researchers describe patient-reported benefits lasting up to five weeks after treatment, and believe the psychedelic compound may effectively reset the activity of key brain circuits known to play a role in depression.

This study was approved by the National Research Ethics Service (NRES) committee London – West London and was conducted in accordance with the revised declaration of Helsinki (2000), the International Committee on Harmonisation Good Clinical Practice (GCP) guidelines and National Health Service (NHS) Research Governance Framework. Imperial College London sponsored the research which was conducted under a Home Office license for research with schedule 1 drugs. The Medicines and Healthcare products Regulatory Agency (MHRA) approved the study. All patients gave written informed consent, consistent with GCP.

Imaging vs clinical outcomes

To explore relationships between significant imaging outcomes and the main clinical outcomes, we chose to focus on changes in depressive symptoms from: 1) pre-Treatment to scan 2 (i.e. one-day post-treatment), and 2) pre-Treatment to 5 weeks post-Treatment. The primary clinical outcome measure, the 16-item Quick Inventory of Depressive Symptoms (QIDS-SR16) was chosen for this purpose. Relationships between imaging outcomes and contemporaneous decreases in depressive symptoms were calculated using a standard Pearson’s r, and relationships with the longer-term (i.e. at 5 weeks post-treatment) changes in depressive symptoms were calculated by splitting the sample into responders (>50% reduction in QIDS-SR16 scores) and non-responders at this time-point, and then performing a one-tailed t-test on the relevant imaging outcomes (one-tailed as directionality was unequivocally implied by the direction of the significant imaging outcome). We used a revised version of the QIDS-SR16 for 24-hour measurement for the post-treatment scan in order to get a contemporaneous, state-related index of depressive symptoms at this time-point.

Lying in a room at Imperial College London, surrounded by low lighting and music, Kirk experienced a vivid recollection of visiting his sick mother before she passed away. “I used to go and see my mum in the hospital quite a lot,” recalls Kirk, a middle-aged computer technician who lives in London (he requested we use only his first name). “And a lot of the time she’d be asleep . . . [but] she’d always sense I was there, and after about five minutes she’d wake up, and we’d interact. I kind of went through that again—but it was a kind of letting go.”

Kirk choked up slightly while retelling his experience. “It’s still a little bit emotional,” he says. “The thing I realized [was that] I didn’t want to let go. I wanted to hold on to the grief, because that was the only connection I had with my mum.”

While this may sound like an ordinary therapy session, it was not what you would typically expect. Kirk was experiencing the effects of a 25-mg dose of psilocybin—the active ingredient in psychedelic “magic” mushrooms—which he had ingested as part of a 2015 clinical trial investigating the drug’s therapeutic potential.